Microbiome and SARS-CoV-2 vaccination
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ABSTRACT:
PROVIDER: PRJEB89915 | ENA |
REPOSITORIES: ENA
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Project description:We generated single-cell transcriptomic and BCR sequencing data of B cells from peripheral blood samples taken from a SARS-CoV-2-antigen-naive cohort being vaccinated with the SARS-CoV-2 mRNA-1273 vaccine. Blood samples were collected at the baseline timepoint D-1 (i.e. one day prior to the initial vaccination), D+5, D+9, D+12, W8 (taken just before the second immunization), W10 and M6 post first vaccination dose. This dataset, in conjunction with other multi-omic data generated from other samples in the study, allowed us to finely map B cell, Class switch recombination (CSR) and antibody production dynamics during primary immunization in the context of vaccine-derived antigen-specific B cells.
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Project description:Healthcare workers were recruited at St Bartholomew’s Hospital, London, UK in the week of lockdown in the United Kingdom (between 23rd and 31st March 2020). Participants underwent weekly evaluation using a questionnaire and biological sample collection (including serological assays) for up to 16 weeks when attending for work and self-declared as fit to attend work at each visit, with further follow up samples collected at 24 weeks. Blood RNA sequencing data was to be used to identify host-response biomarkers of early SARS-CoV-2 infection, to evaluate existing blood transcriptomic signatures of viral infection, and to describe the underlying biology during SARS-CoV-2 infection. This submission includes a total of 172 blood RNA samples from 99 participants. Of these, 114 samples (including 16 convalescent samples collected 6 months after infection) were obtained from 41 SARS-CoV-2 cases, with the remaining 58 from uninfected controls. Participants with available blood RNA samples who had PCR-confirmed SARS-CoV-2 infection during follow-up were included as ‘cases’. Those without evidence of SARS-CoV-2 infection on nasopharyngeal swabs and who remained seronegative by both Euroimmun anti S1 spike protein and Roche anti nucleocapsid protein throughout follow-up were included as uninfected controls. ‘Cases’ include all available RNA samples, including convalescent samples at week 24 of follow-up for a subset of participants. For uninfected controls, we included baseline samples only. Sample class denotes weekly interval to positive SARS-CoV-2 PCR; non-infected controls (NIC); convalescent samples (Conv)_.
2021-07-07 | E-MTAB-10022 | biostudies-arrayexpress
Project description:RNA vaccines are efficient preventive measures to combat the SARS-CoV-2 pandemic. High levels of neutralizing SARS-CoV-2-antibodies are an important component of vaccine-induced immunity. Shortly after the initial two mRNA vaccine doses, the IgG response mainly consists of the pro-inflammatory subclasses IgG1 and IgG3. Here, we report that several months after the second vaccination, SARS-CoV-2-specific antibodies were increasingly composed of non-inflammatory IgG4, which were further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough infections. IgG4 antibodies among all spike-specific IgG antibodies rose on average from 0.04% shortly after the second vaccination to 19.27% late after the third vaccination. This induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. Single-cell sequencing and flow cytometry revealed substantial frequencies of IgG4-switched B cells within the spike-binding memory B-cell population (median 14.4%; interquartile range (ICR) 6.7-18.1%) compared to the overall memory B-cell repertoire (median 1.3%; ICR 0.9-2.2%) after three immunizations. Importantly, this class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition. Since Fc-mediated effector functions are critical for antiviral immunity, these findings may have consequences for the choice and timing of vaccination regimens using mRNA vaccines, including future booster immunizations against SARS-CoV-2.
2022-12-22 | GSE221319 | GEO
Project description:RNA vaccines are efficient preventive measures to combat the SARS-CoV-2 pandemic. High levels of neutralizing SARS-CoV-2-antibodies are an important component of vaccine-induced immunity. Shortly after the initial two mRNA vaccine doses, the IgG response mainly consists of the pro-inflammatory subclasses IgG1 and IgG3. Here, we report that several months after the second vaccination, SARS-CoV-2-specific antibodies were increasingly composed of non-inflammatory IgG4, which were further boosted by a third mRNA vaccination and/or SARS-CoV-2 variant breakthrough infections. IgG4 antibodies among all spike-specific IgG antibodies rose on average from 0.04% shortly after the second vaccination to 19.27% late after the third vaccination. This induction of IgG4 antibodies was not observed after homologous or heterologous SARS-CoV-2 vaccination with adenoviral vectors. Single-cell sequencing and flow cytometry revealed substantial frequencies of IgG4-switched B cells within the spike-binding memory B-cell population (median 14.4%; interquartile range (ICR) 6.7-18.1%) compared to the overall memory B-cell repertoire (median 1.3%; ICR 0.9-2.2%) after three immunizations. Importantly, this class switch was associated with a reduced capacity of the spike-specific antibodies to mediate antibody-dependent cellular phagocytosis and complement deposition. Since Fc-mediated effector functions are critical for antiviral immunity, these findings may have consequences for the choice and timing of vaccination regimens using mRNA vaccines, including future booster immunizations against SARS-CoV-2.
2022-12-22 | GSE221316 | GEO
Project description:γδ T cells provide rapid cellular immunity against pathogens. Here, we conducted matched single-cell RNA-sequencing and γδ-TCR-sequencing to delineate the molecular changes in γδ T cells during a longitudinal study following mRNA SARS-CoV-2 vaccination. While the first dose of vaccine primes Vδ2 T cells, it is the second administration that significantly boosts their immune response. Specifically, the second vaccination uncovers memory features of Vδ2 T cells, shaped by the induction of AP-1 family transcription factors and characterized by a convergent central memory signature, clonal expansion, and an enhanced effector potential. This temporally distinct effector response of Vδ2 T cells was also confirmed in vitro upon stimulation with SARS-CoV-2 spike-peptides. Indeed, the second challenge triggers a significantly higher production of IFNγ by Vδ2 T cells. Collectively, our findings suggest that mRNA SARS-CoV-2 vaccination might benefit from the establishment of long-lasting central memory Vδ2 T cells to confer protection against SARS-CoV-2 infection.
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Project description:Innate immunity triggers responsible for viral control or hyperinflammation in COVID-19 are largely unknown. Recently we could show that the SARS-CoV-2 spike protein (S-protein) primes inflammasome formation and release of mature interleukin-1β (IL-1β) in macrophages derived from COVID-19 patients but not in macrophages from healthy SARS-CoV-2 naïve individuals (Theobald et al. EMBO Mol Med. 2021). Further analysis revealed that SARS-CoV-2 infection causes profound and long-lived reprogramming of macrophages resulting in augmented immunogenicity of the SARS-CoV-2 S-protein, a major vaccine antigen and potent driver of adaptive and innate immune signaling. In this project we want to focus on novel mRNA vaccines, which are exploiting S-protein driven immunogenicity for protection against SARS-CoV-2. Transcriptome analyses of macrophages might reveal differences in innate immune-associated pathways between vaccinated and unvaccinated individuals after prime-boost. Thus, our project could help to gain a better understanding of vaccine-induced immunity including underlying molecular mechanisms in the interaction of the innate and adaptive immune system after mRNA-based SARS-CoV-2 vaccination.
2022-05-02 | GSE200274 | GEO
Project description:The experiment aims at characterizing the immune responses elicited by the BNT162b2 vaccine against SARS-CoV-2, initially administered in a two dose regimen (second dose after three weeks followinf the first dose) In particular the transcriptional landscape of circulating T and B lymphocytes has been profiled longitudinnaly by scRNA-seq coupleD with CITE-seq of 19 cell surface markers to better classify T cells subpopulations, LIBRA-seq to assess the Spike-specificity of BCRs and and V(D)J seq to also track T and B cell clones dynamics. Eeach sample was profiled before vaccination (T0), 21 days after the first dose (T1), 2 months after the first dose (1 month after the second dose) (T2). The immune responses were characterized using PBMC from 3 SARS-CoV-2 experienced donors (experiencing SARS-Cov-2 at least 4 months before the first vaccinatin) and 2 SARS-CoV-2 unexperienced donors.
2024-04-18 | E-MTAB-13721 | biostudies-arrayexpress
Project description:Although mRNA-based COVID-19 vaccines have demonstrated high efficacy, their widespread global use remains constrained by high production costs and cold-chain requirements. Modified vaccinia virus Ankara (MVA) is a highly attenuated and thermostable viral vector with low production costs, potent immunogenicity and strong potential for global distribution. Here, we compared head-to-head the long-term immunogenicity and protective efficacy of an MVA-based vaccine candidate with an approved mRNA vaccine in K18-hACE2 mice, both expressing the SARS-CoV-2 Omicron XBB.1.5 spike (S) protein. Mice received by intramuscular route homologous (mRNA/mRNA and MVA/MVA), heterologous (mRNA/MVA), or single-dose MVA regimens. SARS-CoV-2-specific humoral and cellular responses were evaluated at 10 days and 9 months post-boost, as well as antibody levels at intermediate time points, and protection was assessed following intranasal SARS-CoV-2 XBB.1.5 challenge at 9 months post-vaccination. Binding IgG antibodies against the XBB.1.5 S protein remained high throughout the 9-month period in all vaccinated groups, whereas neutralizing antibody titers peaked early after boosting and progressively declined, converging across regimens over time. S-specific CD8⁺ T-cell responses were strongest in mRNA-containing regimens at day 10 post-boost and, although contracted over time, remain detectable at 9 months post-boost in all two-doses groups, with a trend toward enhanced persistence in the heterologous mRNA/MVA regimen. In contrast, S-specific CD4⁺ T-cell responses remained low across all groups. All two-dose regimens conferred robust protection against SARS-CoV-2 XBB.1.5 challenge, significantly reducing viral RNA levels and infectious titers in both the upper and lower respiratory tract. Transcriptomic analysis of lung tissue after virus challenge revealed that vaccinated animals exhibited reduced expression of genes associated with inflammatory myeloid responses, interferon signalling, and cellular stress compared with infected controls, consistent with attenuated pulmonary inflammation. Notably, mRNA and MVA platforms induced distinct yet convergent protective transcriptional signatures, characterized by a shared reduction of interferon‑driven inflammation alongside differential engagement of humoral versus innate/cellular effector pathways, characteristic of effective antiviral immunity. Overall, our findings demonstrate that MVA‑based vaccination induce durable and protective immunity comparable to mRNA vaccines and support its use as both an alternative and complementary platform to broaden and diversify vaccine‑induced immune responses against SARS-CoV-2 and other emerging respiratory viruses.
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